Modifying a nucleoside, nucleotide or oligonucleotide with a specific chemical functionality, such as a photo-, redox- or chemically-active metal complex, is of wide-spread interest for analytical applications (sequencing, hybridization assays), therapeutic uses (anticancer, antiviral pharmaceuticals) and mechanistic studies (electron transfer, structure-function). U. Englisch, D. D. Gauss, Angew. Chem. Int. Ed. Engl. 30 (1991) 613-629; G. H. Keller, M. M. Manak, DNA Probes, Stockton Press, New York 1993; P. G. Sammes, and G. Yahioglu, Natural Product Reports (1996) 1-28. Synthetic strategies toward these supra-molecular bioassemblies focus primarily on post-modification of the synthesized nucleic acid single strand or complementary duplex. A number of researchers, (C. J. Murphy, M. R. Arkin, J. K. Barton, Science 262 (1993) 1025-1029; R. E. Holmlin, P. J. Dandliker, J. K. Barton, Angew, Chem. Int. Ed. Engl. 36 (1997) 2714-2730 and references therein; D. Magda, R. A. Miller, J. L. Sessler, B. L. Iverson, J. Am. Chem. Soc. 119, (1994) 7439-7440; J. Telser, K. A. Cruickshank. K. S. Schanze, T. L. Netzel. J. Am Chem. Soc. 111 (1989) 7221-7226; W. Bannwarth, D. Schmidt. R. L. Stallard. C. Hornung. R. Knorr, F. Muller, Helv. Chim. Acta 71 (1988) 2085-2099), have used this strategy to link a metal complex, usually as the activated succinimide ester, to the terminus of the nucleic acid single strand previously modified to contain an alkyl amine. In another approach, an amino- or diimine-modified (e.g., phenanthroline) nucleoside is synthesized, and subsequently reacted with a metal to form the desired complex. G. B. Dreyer, P. B. Dervin, Biochemistry 82 (1985) 968-972; C. B. Chen. D. S. Sigman, J. Am. Chem. Soc. 110 (1988) 6570-6572; M. Matsumura. M. Endo, M. Komiyama, J. Chem. Soc., Chem. Commun. (1994) 2019-2020; J. K. Bashkin. E. I. Frolova. U. Sampath, J. Am. Chem. Soc. 116 (1994) 5981-5982; T. J. Meade, J. F. Kayyem. Angew. Chem. Int. Ed. Engl. 34 (1995) 352-354. An alternative strategy that offers clear synthetic advantages over the previous systems is to use DNA/RNA solid-phase synthetic methodologies for the site-specific labeling of an oligonucleotide with a transition metal complex. A number of investigations are currently exploring this approach. J. Schliepe, U. Berghoff, B. Lippert, D. Cech, Angew. Chem. Int. Ed. Engl. 35 (1996) 646-648; R. Manchanda. S. U. Dunham, S. J. Lippard. J. Am. Chem. Soc. 118 (1996) 5144-5145; W. Bannwarth. D. Schmidt, Tetrahedron Letters 30 (1989) 1513-1516; E. Meggers. D. Kusch. B. Giese, Helvetica Chim. Acta 80 (1997) 640-652; D. J. Hurley. Y. Tor. J. Am. Chem. Soc. 120 (1998) 2194-2195).
The present invention provides novel metal-containing purines, pyrimidines, nucleosides and nucleotides, and derivatives thereof, including those which are useful in nucleic acid synthesis, and identification, such as in detection and sequencing. The present invention also provides a new method of labeling purines, pyrimidines, nucleosides, nucleotides and their derivatives during automated or manual synthesis of nucleic acid polymers, such as oligonucleotides, DNA or RNA molecules.